1. Field Of The Invention
This invention is directed to test strip devices and to analytical methods in which they are used. More specifically, this invention relates to test strip devices for determining the presence, absence and/or the amount of a substance in a liquid especially a biological liquid, and most especially blood. The invention includes strips for both clinical chemistry assays and immunoassays. This system accomplishes analysis of samples containing blood cells and other particulate matter with neither the prior separation of the solids from the sample, nor the requirement that excess sample be wiped away from the sample application site.
2. Description Of The Prior Art
The prior art contains an enormous amount of literature directed to analytical test strip devices ranging from simple layered devices of fibrous and non-fibrous materials to multilayered devices of mixed forms of layers such as fibrous and non-fibrous, synthetic or natural materials. Irrespective of the general form taken by the various test strips of the art, they tend to function by allowing the applied sample to migrate to a reaction site where the analyte of interest in the sample reacts with appropriate reactants. The evidence of the reaction is then viewed with the naked eye or through the detection of emitted energy under stimulation such as with a fluorometer, geiger counter, reflectometer, or the like. Some of the earlier systems described are those of U.S. Pat. Nos. 3,061,523 to Free, 3,552,925 to Fetter, 607,093 to Stone, 3,092,465 to Adams, and 3,630,957 to Rey.
In the Free patent a chemistry reagent system for colormetric determination of glucose in biological samples is described. A solid phase test strip is pre-treated with the reactants and thereafter contacted with a sample suspected of containing glucose. The intensity of color developed as a result of the reaction is compared to a control for an indication of the glucose level in the sample.
Fetter discloses a method and device for separating the whole blood sample into its liquid component and its red blood cell and other color forming component by pre-treatment of his test strip with water soluble salts. These salts separate the plasma from the red blood cells so that the plasma is free to wick into the test element.
In Fetter, the same element can be used for both the separating reagents and the reactants specific for the analyte of interest. The whole blood sample would be applied to one side of the strip held horizontally. After adequate penetration of the sample into the test strip, it would be inverted and any color change observed on the bottom of the strip.
U.S. Pat. No. 3,607,093 to Stone describes a liquid permeable membrane having within its matrix, a dry chemistry reagent system. Use of the Stone device requires the physical wiping of excess blood at the sample site of the membrane for removal of cells and other materials.
Lange U.S. Pat. No. 3,802,842 describes a test strip incorporating a dry chemistry reagent system in which a sample receptive surface of an indicator reagent layer is covered by a fine mesh. The indicator layer can be supported upon a colorless and transparent support. The addition of the fine mesh to this test element reportedly results in enhancement in speed and uniformity of distribution of sample upon the surface of the indicator layer. This uniformity of distribution also reportedly results in substantial improvement in reproducibility of result.
U.S. Pat. No. 4,042,335 describes a series of multilayered analytical elements suitable for performing chemical analysis of whole blood samples. They al contemplate the application of test samples either directly, or from a spreading layer, onto a reagent layer.
U.S. Pat. No. 4,144,306 (to Figueras), describes a multi-layered analytical element analogous to that of the Clement patent.
U.S. Pat. No. 4,258,001 to Pierce et al., describes a multi-layered analytical element (of the type described in both Clement and Figueras--previously discussed) incorporating a unique spreading layer. The spreading layer of the Pierce patent is described as an essentially "non-fibrous" material.
The above are only a small sample of various relevant pieces of prior art which relate to the analysis of blood and other liquids. Generally, a multilayer device is encountered, although single layered devices are used as well. More recently there have been single layered membranes used without any separating layers, but these generally allow red blood cells to come through to the reaction site.